Protocol Number: 02-C-0141

Title:

Phase I Trial and Pharmacokinetic Study of ABT-751, An Orally Bioavailable Tubulin Binding Agent, on a 7 Day and 21 Day Dosing Schedule in Pediatric Patients With Refractory Solid Tumors

Number:

02-C-0141

Summary:

This study will determine the safety of the experimental drug ABT-751 in children and young adults with solid tumors and how the body handles this drug. ABT-751 is one of a new class of anticancer drugs that hamper the ability of cancer cells to divide. Other drugs in this class include vincristine, vinblastine, vinorelbine, paclitaxel and docetaxel. In laboratory studies, ABT-751 kills cancer cells that are resistant to vincristine and paclitaxel.

Patients up to 18 years of age with neuroblastoma whose disease does not respond to standard treatment are being enrolled in this study. Candidates are screened with a medical history, physical and neurological examinations, blood and urine tests, electrocardiogram, echocardiogram, and imaging studies.

Participants take ABT-751 by mouth daily for 7 days every 21 days for each treatment cycle. Cycles are repeated every 21 to 28 days, depending on how long it takes the patient to recover from the drug side effects. During treatment, patients undergo the following evaluations:

-Physical examinations weekly and routine blood tests twice a week during the first four treatment cycle, then periodically during the duration of therapy

-MIBG, CT or MRI scans during the first treatment cycle, then before cycles 3 and 5, then every fourth cycle during therapy

-Bone marrow biopsy from the pelvic bones on both sides of the body before starting treatment and, if positive for neuroblastoma, repeated periodically during therapy

-Echocardiogram before starting treatment, then before cycles 3 and 5, then every fourth cycle during therapy

-Daily diary of medications taken each day and record of pain or discomfort for review each cycle

-Blood tests during the first treatment cycle to study how the body handles ABT-751. Five blood samples of are drawn on the first day of ABT-751 therapy, one sample is drawn on day 2 before taking the drug, and one sample is drawn between days 3 and 7 before taking the drug. If possible, blood is drawn through a small plastic catheter placed in a vein (heparin lock or Hickman line or port-a-cath) to avoid multiple needle sticks.

-Blood draws before starting therapy and at various times during the first treatment cycle for research studies

-Magnetic resonance imaging (MRI) with gadolinium contrast before starting the first treatment cycle and again 3 to 7 days after starting treatment to analyze the effect of ABT-751 on blood flow to the tumor. This test is done only in some patients.

Patients may continue treatment unless their disease worsens with ABT-751 or they experience unsafe treatment side effects. When they come off the study, they are evaluated with a physical examination, blood and urine tests and tests to assess tumor size.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: No longer recruiting/follow-up only

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Pharmacokinetics

Pharmacodynamics

Toxicity

Antimitotic Agents

Recruitment Keyword(s):

Cancer

Solid Tumor

Tumor

Children

Pediatrics

Condition(s):

Neoplasms

Investigational Drug(s):

ABT-751

Investigational Device(s):

None

Interventions:

Drug: ABT-751

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Dumontet C, Sikic BI Mechanisms of action of and resistance to antitubulin agents: microtubule dynamics, drug transport, and cell deathJ Clin Oncol 1999 Mar;17(3):1061-70 Review

Funahashi Y, Koyanagi N, Kitoh K Effect of E7010 on liver metastasis and life span of syngeneic C57BL/6 mice bearing orthotopically transplanted murine Colon 38 tumor Cancer Chemother Pharmacol 2001;47(2):179-84

Giannakakou P, Sackett DL, Kang YK, Zhan Z, Buters JT, Fojo T, Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization J Biol Chem 1997 Jul 4;272(27):17118-25

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009